Abstract
Abstract
Introduction: Certain autoimmune and infectious conditions are associated with increased risks of subtypes of non-Hodgkin lymphomas (NHL). A few prior studies suggest that chronic immune stimulation may particularly elevate risk for the NHL subtype lymphoplasmacytic lymphoma (LPL)/Waldenström’s macroglobulinemia (WM). To improve our understanding on the role of immune-related and inflammatory conditions in LPL/WM pathogenesis, we conducted a large population-based study including close to 2,500 LPL/WM patients diagnosed in Sweden and almost 10,000 matched controls.
Methods: Using both the central Cancer registry and local hospital-based registries, we identified all LPL/WM patients diagnosed in Swedish hospitals 1958–2005. From the Swedish Population Registry we identified four matched controls per LPL/WM patient. Through data linkage with the central Inpatient registry, we gathered information on hospital inpatient discharges that listed autoimmune-, infectious-, and other inflammatory/allergic diseases present at least 1 year prior to LPL/WM. Using Poisson regression, we calculated rate ratios (RR) and 95% confidence intervals (CI) adjusted for categorical year of birth, date of diagnosis, gender, and county.
Results: A total of 2,470 LPL/WM patients (647 LPL and 1,823 WM), and 9,698 population-based matched controls were included in the study. We found an increased risk of developing LPL/WM among individuals with a prior history of systemic sclerosis (RR=4.7; 1.4–15.3), Sjögren’s syndrome (RR=12.1; 3.3–45.0), autoimmune hemolytic anemia (AIHA) (RR=24.2; 5.4–108.2), polymyalgia rheumatica (RR=2.9; 1.6–5.2), and temporalis arteritis (RR=8.3; 2.1–33.1). We also found excess risk of LPL/WM among persons with a history of pneumonia (RR=1.4; 1.1–1.7), septicaemia (RR=2.4; 1.2–4.3), pyelonephritis (RR=1.7; 1.1–2.5), sinusitis (RR=2.7; 1.4–4.9), herpes zoster (RR=3.4; 2.0–5.6), and influenza (RR=2.9; 1.7–5.0). Importantly, when we assessed the associations by latency (time between immune-related or inflammatory conditions and LPL/WM), for most autoimmune- and infectious diseases the excess LPL/WM risk remained significant at >5 years latency. We found no significant increased risk for LPL/WM among individuals with prior chronic inflammatory or allergic conditions.
Conclusions: In the largest investigation of risk factors for LPL/WM to date, we found a personal history of certain autoimmune and infectious diseases to be associated with excess LPL/WM risk. Immune-related conditions might act as potential LPL/WM triggers or they could represent premalignant immune disruptions preceding LPL/WM. Our results provide novel insights into the as yet unclear pathogenesis of LPL/WM.